The role of clinical and neuroimaging features in the diagnosis of CADASIL

Lombardia GENS-group, A. Bersano, G. Bedini, H.S. Markus, P. Vitali, E. Colli-Tibaldi, F. Taroni, C. Gellera, S. Baratta, L. Mosca, P. Carrera, M. Ferrari, C. Cereda, G. Grieco, S. Lanfranconi, F. Mazucchelli, D. Zarcone, M.L. De Lodovici, G. Bono, G.B. Boncoraglio & 32 others E.A. Parati, M.V. Calloni, P. Perrone, B.M. Bordo, C. Motto, E. Agostoni, A. Pezzini, Alessandro Padovani, G. Micieli, A. Cavallini, Graziella Molini, Francesco Sasanelli, M. Sessa, G. Comi, Nicoletta Checcarelli, Massimo Camerlingo, M. Corato, S. Marcheselli, Laura Fusi, Giampiero Grampa, Davide Uccellini, S. Beretta, Carlo Ferrarese, Barbara Incorvaia, Carlo Sebastiano Tadeo, Laura Adobbati, V. Silani, Giuseppe Faragò, Nadia Trobia, Caspar Grond-Ginsbach, Livia Candelise, M.T. Bassi

Research output: Contribution to journalArticle

Abstract

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. Methods: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. Results: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
Original languageEnglish
Pages (from-to)2934-2943
Number of pages10
JournalJournal of Neurology
Volume265
Issue number12
DOIs
Publication statusPublished - 2018

Fingerprint

CADASIL
Neuroimaging
Lacunar Stroke
Cerebral Small Vessel Diseases
History
Stroke
Mutation
Gliosis
Genetic Testing
Temporal Lobe
Atrophy
Germany
Dementia
Demography
Genes

Keywords

  • CADASIL
  • Diagnosis
  • Monogenic disorders
  • Neuroimaging
  • NOTCH3 gene
  • Stroke genetics
  • genomic DNA
  • Notch3 receptor
  • NOTCH3 protein, human
  • adult
  • aged
  • Article
  • brain atrophy
  • brain hemorrhage
  • cerebrovascular accident
  • clinical feature
  • dementia
  • demography
  • diagnostic accuracy
  • diagnostic test accuracy study
  • external capsule
  • family history
  • female
  • gene mutation
  • genetic association
  • genetic screening
  • gliosis
  • human
  • lacunar stroke
  • major clinical study
  • male
  • middle aged
  • neuroimaging
  • neuroradiology
  • nuclear magnetic resonance imaging
  • predictive value
  • priority journal
  • sensitivity and specificity
  • stroke patient
  • temporal lobe
  • thalamus
  • transient ischemic attack
  • white matter
  • white matter lesion
  • atrophy
  • brain
  • diagnostic imaging
  • genetics
  • pathophysiology
  • prospective study
  • Adult
  • Aged
  • Atrophy
  • Brain
  • Cerebral Hemorrhage
  • Female
  • Humans
  • Ischemic Attack, Transient
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prospective Studies
  • Receptor, Notch3
  • Stroke, Lacunar
  • White Matter

Cite this

Lombardia GENS-group, Bersano, A., Bedini, G., Markus, H. S., Vitali, P., Colli-Tibaldi, E., ... Bassi, M. T. (2018). The role of clinical and neuroimaging features in the diagnosis of CADASIL. Journal of Neurology, 265(12), 2934-2943. https://doi.org/10.1007/s00415-018-9072-8

The role of clinical and neuroimaging features in the diagnosis of CADASIL. / Lombardia GENS-group; Bersano, A.; Bedini, G.; Markus, H.S.; Vitali, P.; Colli-Tibaldi, E.; Taroni, F.; Gellera, C.; Baratta, S.; Mosca, L.; Carrera, P.; Ferrari, M.; Cereda, C.; Grieco, G.; Lanfranconi, S.; Mazucchelli, F.; Zarcone, D.; De Lodovici, M.L.; Bono, G.; Boncoraglio, G.B.; Parati, E.A.; Calloni, M.V.; Perrone, P.; Bordo, B.M.; Motto, C.; Agostoni, E.; Pezzini, A.; Padovani, Alessandro; Micieli, G.; Cavallini, A.; Molini, Graziella; Sasanelli, Francesco; Sessa, M.; Comi, G.; Checcarelli, Nicoletta; Camerlingo, Massimo; Corato, M.; Marcheselli, S.; Fusi, Laura; Grampa, Giampiero; Uccellini, Davide; Beretta, S.; Ferrarese, Carlo; Incorvaia, Barbara; Tadeo, Carlo Sebastiano; Adobbati, Laura; Silani, V.; Faragò, Giuseppe; Trobia, Nadia; Grond-Ginsbach, Caspar; Candelise, Livia; Bassi, M.T.

In: Journal of Neurology, Vol. 265, No. 12, 2018, p. 2934-2943.

Research output: Contribution to journalArticle

Lombardia GENS-group, Bersano, A, Bedini, G, Markus, HS, Vitali, P, Colli-Tibaldi, E, Taroni, F, Gellera, C, Baratta, S, Mosca, L, Carrera, P, Ferrari, M, Cereda, C, Grieco, G, Lanfranconi, S, Mazucchelli, F, Zarcone, D, De Lodovici, ML, Bono, G, Boncoraglio, GB, Parati, EA, Calloni, MV, Perrone, P, Bordo, BM, Motto, C, Agostoni, E, Pezzini, A, Padovani, A, Micieli, G, Cavallini, A, Molini, G, Sasanelli, F, Sessa, M, Comi, G, Checcarelli, N, Camerlingo, M, Corato, M, Marcheselli, S, Fusi, L, Grampa, G, Uccellini, D, Beretta, S, Ferrarese, C, Incorvaia, B, Tadeo, CS, Adobbati, L, Silani, V, Faragò, G, Trobia, N, Grond-Ginsbach, C, Candelise, L & Bassi, MT 2018, 'The role of clinical and neuroimaging features in the diagnosis of CADASIL', Journal of Neurology, vol. 265, no. 12, pp. 2934-2943. https://doi.org/10.1007/s00415-018-9072-8
Lombardia GENS-group, Bersano A, Bedini G, Markus HS, Vitali P, Colli-Tibaldi E et al. The role of clinical and neuroimaging features in the diagnosis of CADASIL. Journal of Neurology. 2018;265(12):2934-2943. https://doi.org/10.1007/s00415-018-9072-8
Lombardia GENS-group ; Bersano, A. ; Bedini, G. ; Markus, H.S. ; Vitali, P. ; Colli-Tibaldi, E. ; Taroni, F. ; Gellera, C. ; Baratta, S. ; Mosca, L. ; Carrera, P. ; Ferrari, M. ; Cereda, C. ; Grieco, G. ; Lanfranconi, S. ; Mazucchelli, F. ; Zarcone, D. ; De Lodovici, M.L. ; Bono, G. ; Boncoraglio, G.B. ; Parati, E.A. ; Calloni, M.V. ; Perrone, P. ; Bordo, B.M. ; Motto, C. ; Agostoni, E. ; Pezzini, A. ; Padovani, Alessandro ; Micieli, G. ; Cavallini, A. ; Molini, Graziella ; Sasanelli, Francesco ; Sessa, M. ; Comi, G. ; Checcarelli, Nicoletta ; Camerlingo, Massimo ; Corato, M. ; Marcheselli, S. ; Fusi, Laura ; Grampa, Giampiero ; Uccellini, Davide ; Beretta, S. ; Ferrarese, Carlo ; Incorvaia, Barbara ; Tadeo, Carlo Sebastiano ; Adobbati, Laura ; Silani, V. ; Faragò, Giuseppe ; Trobia, Nadia ; Grond-Ginsbach, Caspar ; Candelise, Livia ; Bassi, M.T. / The role of clinical and neuroimaging features in the diagnosis of CADASIL. In: Journal of Neurology. 2018 ; Vol. 265, No. 12. pp. 2934-2943.
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title = "The role of clinical and neuroimaging features in the diagnosis of CADASIL",
abstract = "Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. Methods: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. Results: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5{\%} of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield. {\circledC} 2018, Springer-Verlag GmbH Germany, part of Springer Nature.",
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author = "{Lombardia GENS-group} and A. Bersano and G. Bedini and H.S. Markus and P. Vitali and E. Colli-Tibaldi and F. Taroni and C. Gellera and S. Baratta and L. Mosca and P. Carrera and M. Ferrari and C. Cereda and G. Grieco and S. Lanfranconi and F. Mazucchelli and D. Zarcone and {De Lodovici}, M.L. and G. Bono and G.B. Boncoraglio and E.A. Parati and M.V. Calloni and P. Perrone and B.M. Bordo and C. Motto and E. Agostoni and A. Pezzini and Alessandro Padovani and G. Micieli and A. Cavallini and Graziella Molini and Francesco Sasanelli and M. Sessa and G. Comi and Nicoletta Checcarelli and Massimo Camerlingo and M. Corato and S. Marcheselli and Laura Fusi and Giampiero Grampa and Davide Uccellini and S. Beretta and Carlo Ferrarese and Barbara Incorvaia and Tadeo, {Carlo Sebastiano} and Laura Adobbati and V. Silani and Giuseppe Farag{\`o} and Nadia Trobia and Caspar Grond-Ginsbach and Livia Candelise and M.T. Bassi",
note = "Export Date: 17 January 2019 CODEN: JNRYA Correspondence Address: Bersano, A.; Cerebrovascular Unit, Neurological Institute “C. Besta” IRCCS Foundation, Via Celoria 11, Italy; email: anna.bersano@gmail.com Chemicals/CAS: NOTCH3 protein, human; Receptor, Notch3 Funding details: Regione Lombardia Funding details: National Institute for Health Research, NIHR Funding details: VIII/006128-12/12/2007 Funding text 1: Funding The Lombardia GENS project has received funding from the Regione Lombardia Government as a Research Independent Project (DGR n°VIII/006128-12/12/2007). Lombardia GENS is an investigator-driven, academic, non-profit consortium and is publicly funded. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Biomedical Research Centre. References: Joutel, A., Corpechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Tournier-Lasserve, E., Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia (1996) Nature, 383, pp. 707-710. , COI: 1:CAS:528:DyaK28XmsVGnsro{\%}3D; Dichgans, M., Mayer, M., Uttner, I., Br{\"u}ning, R., M{\"u}ller-H{\"o}cker, J., Rungger, G., Ebke, M., Gasser, T., The phenotypic spectrum of CADASIL: clinical findings in 102 cases (1998) Ann Neurol, 44, pp. 731-739. , COI: 1:STN:280:DyaK1M{\%}2FjsVagtQ{\%}3D{\%}3D; Opherk, C., Peters, N., Herzog, J., Luedtke, R., Dichgans, M., Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients (2004) Brain, 127, pp. 2533-2539; Chabriat, H., Levy, C., Taillia, H., Iba-Zizen, M.T., Vahedi, K., Joutel, A., Tournier-Lasserve, E., Bousser, M.G., Patterns of MRI lesions in CADASIL (1998) Neurology, 51, pp. 452-457. , COI: 1:STN:280:DyaK1czntlOqsA{\%}3D{\%}3D; Singhal, S., Rich, P., Markus, H.S., The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features (2005) AJNR Am J Neuroradiol, 26, pp. 2481-2487. , PID: 16286388; Joutel, A., Corpechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Tournier-Lasserve, E., Notch3 mutations in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a mendelian condition causing stroke and vascular dementia (1997) Ann N Y Acad Sci, 826, pp. 213-217. , COI: 1:CAS:528:DyaK2sXmvFyltr8{\%}3D; Artavanis-Tsakonas, S., Matsuno, K., Fortini, M.E., Notch signaling (1995) Science, 268, pp. 225-232. , COI: 1:CAS:528:DyaK2MXltVCitLg{\%}3D; Choi, J.C., Song, S.K., Lee, J.S., Kang, S.Y., Kang, J.H., Diversity of stroke presentation in CADASIL: study from patients harboring the predominant NOTCH3 mutation R544C (2013) J Stroke Cerebrovasc Dis, 22, pp. 126-131; Pantoni, L., Pescini, F., Nannucci, S., Sarti, C., Bianchi, S., Dotti, M.T., Federico, A., Pantoni, L., Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative patients (2010) Neurology, 74, pp. 57-63. , COI: 1:STN:280:DC{\%}2BD1Mfksl2gtQ{\%}3D{\%}3D; 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Liu, X., Zuo, Y., Sun, W., Zhang, W., Lv, H., Huang, Y., Xiao, J., Wang, Z., The genetic spectrum and the evaluation of CADASIL screening scale in Chinese patients with NOTCH3 mutations (2015) J Neurol Sci, 354, pp. 63-69. , COI: 1:CAS:528:DC{\%}2BC2MXosVCnsLs{\%}3D; Ince, B., Benbir, G., Siva, A., Saip, S., Utku, U., Celik, Y., Necioglu-Orken, D., Uyguner, O., Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey (2014) Eur Neurol, 72, pp. 125-131; Viswanathan, A., Godin, O., Jouvent, E., O’Sullivan, M., Gschwendtner, A., Peters, N., Duering, M., Chabriat, H., Impact of MRI markers in subcortical vascular dementia: a multi-modal analysis in CADASIL (2010) Neurobiol Aging, 31, pp. 1629-1636; Chabriat, H., Herv{\'e}, D., Duering, M., Godin, O., Jouvent, E., Opherk, C., Alili, N., Dichgans, M., Predictors of clinical worsening in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: prospective cohort study (2016) Stroke, 47, pp. 4-11; Peters, N., Holtmannsp{\"o}tter, M., Opherk, C., Gschwendtner, A., Herzog, J., S{\"a}mann, P., Dichgans, M., Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease (2006) Neurology, 66, pp. 1517-1522. , COI: 1:STN:280:DC{\%}2BD283ovVKhsg{\%}3D{\%}3D; Liem, M.K., Lesnik Oberstein, S.A., Haan, J., van der Neut, I.L., Ferrari, M.D., van Buchem, M.A., Middelkoop, H.A., Lesnik Oberstein, S.A., MRI correlates of cognitive decline in CADASIL: a 7-year follow-up study (2009) Neurology, 72, pp. 143-148. , COI: 1:STN:280:DC{\%}2BD1M{\%}2Fms12ltA{\%}3D{\%}3D",
year = "2018",
doi = "10.1007/s00415-018-9072-8",
language = "English",
volume = "265",
pages = "2934--2943",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "Dr. Dietrich Steinkopff Verlag GmbH and Co. KG",
number = "12",

}

TY - JOUR

T1 - The role of clinical and neuroimaging features in the diagnosis of CADASIL

AU - Lombardia GENS-group

AU - Bersano, A.

AU - Bedini, G.

AU - Markus, H.S.

AU - Vitali, P.

AU - Colli-Tibaldi, E.

AU - Taroni, F.

AU - Gellera, C.

AU - Baratta, S.

AU - Mosca, L.

AU - Carrera, P.

AU - Ferrari, M.

AU - Cereda, C.

AU - Grieco, G.

AU - Lanfranconi, S.

AU - Mazucchelli, F.

AU - Zarcone, D.

AU - De Lodovici, M.L.

AU - Bono, G.

AU - Boncoraglio, G.B.

AU - Parati, E.A.

AU - Calloni, M.V.

AU - Perrone, P.

AU - Bordo, B.M.

AU - Motto, C.

AU - Agostoni, E.

AU - Pezzini, A.

AU - Padovani, Alessandro

AU - Micieli, G.

AU - Cavallini, A.

AU - Molini, Graziella

AU - Sasanelli, Francesco

AU - Sessa, M.

AU - Comi, G.

AU - Checcarelli, Nicoletta

AU - Camerlingo, Massimo

AU - Corato, M.

AU - Marcheselli, S.

AU - Fusi, Laura

AU - Grampa, Giampiero

AU - Uccellini, Davide

AU - Beretta, S.

AU - Ferrarese, Carlo

AU - Incorvaia, Barbara

AU - Tadeo, Carlo Sebastiano

AU - Adobbati, Laura

AU - Silani, V.

AU - Faragò, Giuseppe

AU - Trobia, Nadia

AU - Grond-Ginsbach, Caspar

AU - Candelise, Livia

AU - Bassi, M.T.

N1 - Export Date: 17 January 2019 CODEN: JNRYA Correspondence Address: Bersano, A.; Cerebrovascular Unit, Neurological Institute “C. Besta” IRCCS Foundation, Via Celoria 11, Italy; email: anna.bersano@gmail.com Chemicals/CAS: NOTCH3 protein, human; Receptor, Notch3 Funding details: Regione Lombardia Funding details: National Institute for Health Research, NIHR Funding details: VIII/006128-12/12/2007 Funding text 1: Funding The Lombardia GENS project has received funding from the Regione Lombardia Government as a Research Independent Project (DGR n°VIII/006128-12/12/2007). Lombardia GENS is an investigator-driven, academic, non-profit consortium and is publicly funded. Hugh Markus is supported by an NIHR Senior Investigator award and his work is supported by the Cambridge University Hospitals NIHR Biomedical Research Centre. References: Joutel, A., Corpechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Tournier-Lasserve, E., Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia (1996) Nature, 383, pp. 707-710. , COI: 1:CAS:528:DyaK28XmsVGnsro%3D; Dichgans, M., Mayer, M., Uttner, I., Brüning, R., Müller-Höcker, J., Rungger, G., Ebke, M., Gasser, T., The phenotypic spectrum of CADASIL: clinical findings in 102 cases (1998) Ann Neurol, 44, pp. 731-739. , COI: 1:STN:280:DyaK1M%2FjsVagtQ%3D%3D; Opherk, C., Peters, N., Herzog, J., Luedtke, R., Dichgans, M., Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients (2004) Brain, 127, pp. 2533-2539; Chabriat, H., Levy, C., Taillia, H., Iba-Zizen, M.T., Vahedi, K., Joutel, A., Tournier-Lasserve, E., Bousser, M.G., Patterns of MRI lesions in CADASIL (1998) Neurology, 51, pp. 452-457. , COI: 1:STN:280:DyaK1czntlOqsA%3D%3D; Singhal, S., Rich, P., Markus, H.S., The spatial distribution of MR imaging abnormalities in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and their relationship to age and clinical features (2005) AJNR Am J Neuroradiol, 26, pp. 2481-2487. , PID: 16286388; 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PY - 2018

Y1 - 2018

N2 - Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. Methods: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. Results: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

AB - Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. Methods: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. Results: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. Conclusions: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

KW - CADASIL

KW - Diagnosis

KW - Monogenic disorders

KW - Neuroimaging

KW - NOTCH3 gene

KW - Stroke genetics

KW - genomic DNA

KW - Notch3 receptor

KW - NOTCH3 protein, human

KW - adult

KW - aged

KW - Article

KW - brain atrophy

KW - brain hemorrhage

KW - cerebrovascular accident

KW - clinical feature

KW - dementia

KW - demography

KW - diagnostic accuracy

KW - diagnostic test accuracy study

KW - external capsule

KW - family history

KW - female

KW - gene mutation

KW - genetic association

KW - genetic screening

KW - gliosis

KW - human

KW - lacunar stroke

KW - major clinical study

KW - male

KW - middle aged

KW - neuroimaging

KW - neuroradiology

KW - nuclear magnetic resonance imaging

KW - predictive value

KW - priority journal

KW - sensitivity and specificity

KW - stroke patient

KW - temporal lobe

KW - thalamus

KW - transient ischemic attack

KW - white matter

KW - white matter lesion

KW - atrophy

KW - brain

KW - diagnostic imaging

KW - genetics

KW - pathophysiology

KW - prospective study

KW - Adult

KW - Aged

KW - Atrophy

KW - Brain

KW - Cerebral Hemorrhage

KW - Female

KW - Humans

KW - Ischemic Attack, Transient

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Prospective Studies

KW - Receptor, Notch3

KW - Stroke, Lacunar

KW - White Matter

U2 - 10.1007/s00415-018-9072-8

DO - 10.1007/s00415-018-9072-8

M3 - Article

VL - 265

SP - 2934

EP - 2943

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

IS - 12

ER -